使用包含锌结合基团的 Fmoc 氨基酸合成 HDAC 底物肽模拟抑制剂。
Synthesis of HDAC Substrate Peptidomimetic Inhibitors Using Fmoc Amino Acids Incorporating Zinc-Binding Groups.
机构信息
School of Chemistry , University of Glasgow , Joseph Black Building, University Avenue , Glasgow G12 8QQ , U.K.
Leicester Institute of Structural and Chemical Biology, Department of Molecular and Cell Biology , University of Leicester , Leicester LE1 7RH , U.K.
出版信息
Org Lett. 2019 May 3;21(9):3178-3182. doi: 10.1021/acs.orglett.9b00885. Epub 2019 Apr 18.
Syntheses of Fmoc amino acids having zinc-binding groups were prepared and incorporated into substrate inhibitor H3K27 peptides using Fmoc/Bu solid-phase peptide synthesis (SPPS). Peptide 11, prepared using Fmoc-Asu(NHOBu)-OH, is a potent inhibitor (IC = 390 nM) of the core NuRD corepressor complex (HDAC1-MTA1-RBBP4). The Fmoc amino acids have the potential to facilitate the rapid preparation of substrate peptidomimetic inhibitor (SPI) libraries in the search for selective HDAC inhibitors.
合成了具有锌结合基团的 Fmoc 氨基酸，并通过 Fmoc/Bu 固相肽合成（SPPS）将其掺入到底物抑制剂 H3K27 肽中。使用 Fmoc-Asu（NHOBu）-OH 制备的肽 11 是核 NuRD 共抑制复合物（HDAC1-MTA1-RBBP4）的有效抑制剂（IC = 390 nM）。Fmoc 氨基酸有可能促进用于寻找选择性 HDAC 抑制剂的底物肽模拟抑制剂（SPI）文库的快速制备。
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